The focus of this project is the use of MRI to understand the pathophysiology of multiple sclerosis (MS) and to determine whether disease activity is altered by various immunomodulatory treatments and to investigate the natural history of lesions. In a relatively small cohort of patients being treated with interferon beta-1b we have observed that high neutralizing antibody (Nab) titers to interferon may affect disease activity as determined by MRI but does not seem to alter MS disease progression when compared to patients not developing Nabs. T1- black holes (BHs) on MRI represent either areas of edema, axonal loss or astrogliosis and correlate with disability in patients with MS. We investigated the heterogeneity of BHs' appearance over 48 consecutive months in relapsing remitting MS patients, the role of contrast enhancing lesions (CEL) on BHs' formation, (iii) the role of CEL duration on BHs' duration over time and observed that formation of BHs is related to the amount of CEL. However the duration of BH once those lesions have been formed is most likely a consequence of the duration of the enhancement and blood brain barrier disruption. This new observation on persistent BH overtime indicated that it is possible that axonal loss and gliotic scars can resolve on MRI about 21 months following their initial appearance coinciding with an acute inflammatory lesion.